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Nuclear biomechanics in cancer biology

Project ID: 2228cd1334 (You will need this ID for your application)

Under Offer

Research Theme: Physical Sciences

UCL Lead department: Lab for Molecular Cell Bio

Department Website

Lead Supervisor: Robertus De Bruin

Project Summary:

Changes to the shape and size of nuclei are a common and widespread feature of cancer cells. These changes are so consistent that morphologic abnormalities of the nucleus have been used to distinguish tumour tissue from healthy tissue for over a century. However, it still remains unclear what drives these changes and how these affect the mechanical properties of the nucleus and genome stability A better understanding of this will help identify pathways that could be targeted to potentially prevent cancer initiation and development. Our preliminary data suggests that dysregulation of nuclear morphology is a phenomenon that occurs very early in the oncogenic process, and represents an important driver of genome instability, indicating a potential role in cancer initiation and development. The PhD project aims to elucidate the mechanisms driving cancer-associated changes in nuclear architecture and establish how these affects the mechanical properties of the nucleus and genome stability. You will be trained in our multidisciplinary approaches, including molecular and cell biology, genomics, and biophysics. You will be working closely with a postdoc or senior PhD student in the lab, who will provide daily supervision for practical training. In addition, weekly one-on-one sessions and lab meetings with Professor de Bruin will ensure research project progression and the development of critical thinking, the overarching aim of a PhD. You will investigate how nuclear shape and structure changes upon oncogene activation and how these changes affect mechanical properties, engineering microfabricated devices that allow 2D and 3D cellular confinement to establish how sensitive structurally altered nuclei are to mechanical stress. Overall, the range of techniques will include genetics, live cell-imaging, automated image analysis, experimental biophysics, engineering, and computational modelling. We are looking for a motivated student, interested in being trained in multidisciplinary approaches with a keen interest in biomechanics in cancer biology.